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Oxidative stress induces p53‐dependent apoptosis in hepatoblastoma cell through its nuclear translocation
Author(s) -
Yamamoto Hideki,
Ozaki Toshinori,
Nakanishi Mitsuru,
Kikuchi Hironobu,
Yoshida Kaori,
Horie Hiroshi,
Kuwano Hiroyuki,
Nakagawara Akira
Publication year - 2007
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2007.01065.x
Subject(s) - biology , hepatoblastoma , cytoplasm , apoptosis , oxidative stress , transactivation , programmed cell death , gene knockdown , cancer research , microbiology and biotechnology , chromosomal translocation , transcription factor , gene , genetics , endocrinology , medicine
Hepatoblastoma (HBL) is the most common malignant liver tumor in children. Since tumor suppressor p53 is rarely mutated in HBL, it remains unknown whether p53 could contribute to the hepatocarcinogenesis. In the present study, we have found for the first time that, like neuroblastoma (NBL), wild‐type p53 was abnormally accumulated in the cytoplasm of the human HBL‐derived Huh6 cells. In accordance with this notion, immunohistochemical analysis demonstrated that p53 is largely expressed in cytoplasm of human primary HBLs. In response to the oxidative stress, Huh6 cells underwent apoptotic cell death in association with the nuclear translocation of p53 and the transactivation of its target gene implicated in apoptotic cell death. siRNA‐mediated knockdown of the endogenous p53 conferred the resistance of Huh6 cells to oxidative stress. Intriguingly, histone deacetylase inhibitor (nicotinamide) treatment strongly inhibited the oxidative stress‐induced nuclear translocation of p53 as well as the p53‐dependent apoptosis in Huh6 cells. In contrast to the previous observations, the cytoplasmic anchor protein for p53 termed Parc had undetectable effect on the cytoplasmic retention of p53. Collectively, our present results suggest that the abnormal cytoplasmic localization of p53 might contribute at least in part to the development of HBL.